Chronic graft-versus-host disease (GVHD) is a frequent and often fatal sequela of human allogeneic bone marrow transplantation with features of scleroderma, Sjogren's syndrome and chronic active hepatitis. We have observed a very similar disease developing spontaneously in rat radiation chimeras. We have been able to induce chronic GVHD rapidly and consistently by two alterative methods: sublethal irradiation of chimeras followed by a booster bone marrow transplant and by adoptive transfer of chimera marrow and lymphocytes into third party irradiated recipients. Histology reveals dense dermal collagenosis, lymphoplasmacytic infiltrate and injury of the salivary and lacrinal gland ducts and chronic hepatitis with bile duct injury. Preliminary immunopathological studies suggest the presence of both allogeneic and organ-specific antibodies. This model has excellent potential for the study of the pathogenesis of chronic GVHD, a pre-clinical model for modes of therapy and prevention of chronic GVHD, and of probable value for studying some autoimmune disorders. We plan to thoroughly characterize the histopathology, distinguishing the disease from effects of aging, irradiation and infections. Immunopathological characterization will include definition of humoral and cellular components, antigen specificity of acid eluates of target organs and separation of the reactions against histocompatibility antigens for reaction against organ-specific antigens.